Diabetes is a condition in which a glucose concentration in blood (blood glucose level) has increased abnormally, and suitable control of a blood glucose level is required. A typical therapeutic agent for diabetes is a sulfonylurea agent (hereinafter described as an SU agent), which is also used concomitantly with other therapeutic agent for diabetes. However, it is known that the SU agent causes hypoglycemia as a side effect. Furthermore, it is also concerned that use of the SU agent for a long period leads to fatigue of pancreatic β cells.
An example of hormones which are involved in the change of a glucose concentration in blood may include glucagon-like peptide-1 (hereinafter described as GLP-1) and gastric inhibitory peptide (hereinafter described as GIP). GLP-1 and GIP are a peptide which is secreted from a gastrointestinal tract with a diet, acts on pancreatic βcells to accelerate blood glucose-dependent insulin secretion, and maintains homeostasis of glucose metabolism via acceleration of the generation and secretion of insulin based on the protection or improvement of the function of βcells, suppression of the secretion of glucagon, retardation of gastric emptying, and the like, whereby leads to enhancement of an effect of insulin in the periphery. However, since GLP-1 and GIP are rapidly decomposed by dipeptidyl peptidase IV (hereinafter described as DPP-IV) in circulating blood and inactivated, it may not exhibit its effect sufficiently in vivo.
DPP-IV inhibitors suppress the metabolism of endogenous GLP-1 and GIP, and retain the effect of these. Therefore, they show promise for blood glucose concentration-dependent therapeutic agents for type 2 diabetes, and an effect of protecting pancreatic βcells, which seems to be caused by increase in the concentration of active GLP-1 and GIP, is expected in a long-term administration.
However, since it is considered that acceleration of insulin secretion by GIP is diminished in a patient with type 2 diabetes, the contribution of GIP to the effect of the DPP-IV inhibitor to accelerate insulin secretion in the patient is unclear. On the other hand, it is suggested by studies using receptor gene-deficient animals and the like that GIP may induce obesity or evoke insulin resistance.
For DPP-IV inhibitors, a treatment method for trying to control blood glucose by concomitant use with other diabetic medicine is known (Patent Document 1). For example, there has been reported that approaches to control blood glucose by concomitant use of E3024 trifluoro acetate, which is a DPP-IV inhibitor, with Voglibose (Non-patent Document 1), concomitant use of LAF237 with Metformin (Non-patent Document 2), concomitant use of    2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-4-fluorobenzonitrile or 2-[2-(3-(R)-aminopiperidin-1-yl)-5-fluoro-6-oxo-6H-pyrimidi n-1-ylmethyl]benzonitrile with Voglibose (Patent Document 2), and concomitant use of    3-{2S,4S}-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperadin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine with Voglibose (Patent Document 3).
However, they all relate to concomitant use of a specific compound having a DPP-IV inhibitory effect and other diabetic medicine, and a specific description and an effect of treating diabetes with respect to concomitant use of (S)—N-(2-(2-(2-cyanopyrrolidin-1-yl)-2-oxoethylamino)-2-met hylpropyl)-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide or an analogue thereof as a DPP-IV inhibitor and other diabetic medicine are not known.    Patent Document 1: WO01/052825    Patent Document 2: WO2007/074884    Patent Document 3: WO2006/129785    Non-patent Document 1: Yamazaki, K. et al., Journal of Pharmacological Sciences, 104, 29-38 (2007).    Non-patent Document 2: Ahren, B. et al., Diabetes Care, 27, 2874-80 (2004).